Human beta-defensin-3 promotes wound healing in infected diabetic wounds

Tobias Hirsch, Malte Spielmann, Baraa Zuhaili, Magdalena Fossum, Marie Metzig, Till Koehler, Hans Ulrich Steinau, Feng Yao, Andrew Bruce Onderdonk, Lars Steinstraesser, Elof Eriksson

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds. Methods: Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation. Results: hBD-3-treated wounds showed a total bacterial load of 2.1 × 108 colony-forming units (CFU)/g tissue, versus 1.3 × 109 CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 ± 15% wound closure for hBD-3 expressing wounds and 50 ± 16% for controls (p < 0.01). hBD-3 expression was in the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 × 109 Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3. Conclusions: In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta-defensin-3 may play a major role in diabetic wound healing and wound infections.

Original languageEnglish (US)
Pages (from-to)220-228
Number of pages9
JournalJournal of Gene Medicine
Volume11
Issue number3
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Bacterial infection
  • Gene transfer
  • Host defense peptides
  • Innate immunity
  • S. aureus
  • Wound healing

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

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